Efeito da anestesia com propofol na bioenergética mitocondrial e stresse oxidativo no fígado de rato
Ficheiros
Data
2014-02-04
Autores
Título da revista
ISSN da revista
Título do Volume
Editora
Resumo
Objetivos: O propofol (2,6-diisopropilfenol) é um potente anestésico intravenoso (i.v.) que é predominantemente metabolizado no fígado, podendo causar hepatotoxicidade afetando a bioenergética mitocondrial. Contudo, os mecanismos moleculares pelo qual o propofol induz hepatotoxicidade não foram totalmente elucidados. O objetivo deste trabalho foi investigar o efeito da anestesia com propofol utilizando duas doses clínicas (25 e 62,5 mg/kg/h) ao nível da bioenergética mitocondrial e ao nível das enzimas hepáticas relacionadas com biomarcadores do stresse oxidativo, comparando com um grupo controlo.
Principais métodos: Isolamento de mitocôndrias hepáticas de cada tratamento, sendo posteriormente avaliados os parâmetros respiratórios pelo consumo de oxigénio, assim como, o potencial de membrana (ΔΨ) mitocondrial, acumulação de Ca2+ extramitocondrial, atividade dos complexos mitocondriais e atividades antioxidantes enzimáticas (CAT SOD, GR, GST). Biomarcadores do stresse oxidativo também foram avaliados (GSH/GSSG e LPO).
Principais resultados: O potencial de membrana mitocondrial diminuiu proporcionalmente ao aumento da concentração de propofol. As mitocôndrias da dose mais alta de propofol apresentaram uma menor capacidade em acumular cálcio. Não se observaram diferenças na razão GSH/GSSG entre o controlo e os dois tratamentos.
Conclusão: Os resultados deste estudo apoiam a hipótese de que a anestesia com propofol induz uma sobrecarga de cálcio e uma lesão hepática através de um mecanismo dependente da transição de permeabilidade mitocondrial (MPT).
Aims: Propofol (2,6-diisopropylphenol) is a potent intravenous (i.v.) anaesthetic which is predominately hepatically metabolized. However it can cause hepatotoxicity by affecting mitochondrial bioenergetics. So far, the molecular mechanisms for propofol-induced hepatotoxicity have not been fully elucidated. The aim of the present work was to investigate the action of propofol anaesthesia with two clinical doses (25 and 62.5 mg/kg/h) in mitochondrial rat liver and also evaluate the effect of propofol in liver enzymes related to oxidative stress biomarkers and compare with control animals. Main methods: Liver mitochondria for each treatment were isolated and respiratory parameters evaluated by oxygen consumption, as well measured mitochondrial transmembrane potential (ΔΨ), extramitochondrial free Ca2+, mitochondrial enzyme activities and enzymatic antioxidant activities (SOD, CAT, GR, GST). Oxidative stress biomarkers were also evaluated (GSH/GSSG and LPO). Key findings: Mitochondrial transmembrane electric potential was decreased by propofol in a concentration dependent manner. The mitochondria treated with the highest propofol show a lower capacity to accumulate calcium. No difference was observed in the evaluation of GSH/GSSG ratio between the two treatments and control. Significance: The results of this study support the hypothesis that propofol anaesthesia induces calcium overload and liver injury via a mechanism dependent on mitochondrial permeability transition (MPT).
Aims: Propofol (2,6-diisopropylphenol) is a potent intravenous (i.v.) anaesthetic which is predominately hepatically metabolized. However it can cause hepatotoxicity by affecting mitochondrial bioenergetics. So far, the molecular mechanisms for propofol-induced hepatotoxicity have not been fully elucidated. The aim of the present work was to investigate the action of propofol anaesthesia with two clinical doses (25 and 62.5 mg/kg/h) in mitochondrial rat liver and also evaluate the effect of propofol in liver enzymes related to oxidative stress biomarkers and compare with control animals. Main methods: Liver mitochondria for each treatment were isolated and respiratory parameters evaluated by oxygen consumption, as well measured mitochondrial transmembrane potential (ΔΨ), extramitochondrial free Ca2+, mitochondrial enzyme activities and enzymatic antioxidant activities (SOD, CAT, GR, GST). Oxidative stress biomarkers were also evaluated (GSH/GSSG and LPO). Key findings: Mitochondrial transmembrane electric potential was decreased by propofol in a concentration dependent manner. The mitochondria treated with the highest propofol show a lower capacity to accumulate calcium. No difference was observed in the evaluation of GSH/GSSG ratio between the two treatments and control. Significance: The results of this study support the hypothesis that propofol anaesthesia induces calcium overload and liver injury via a mechanism dependent on mitochondrial permeability transition (MPT).
Descrição
Dissertação de Mestrado em Biologia Clínica Laboratorial
Palavras-chave
Propofol , Anestesia , Bioenergética , Mitocôndrias de fígado de rato , Stresse oxidativo